1. Field Of The Invention
The invention relates to a process for the production of 3-oxocarboxylic acid esters from acetoacetic acid esters.
2. Prior Art
3-Oxocarboxylic acid esters (acylacetic acid esters) of the general formula: ##STR1## are extraordinarily important and versatile intermediate products. This fact is attributable to the numerous different reaction possibilities of these compounds. Their coupling with aromatic diazonium salts thus yields 2-(arylhydrazono)-3-oxocarboxylic acid esters, which are used as dyes, for example, in photographic materials.
With hydrazines, the 3-oxocarboxylic acid esters cyclize to pyrazolones, of which several are valuable pharmaceutical active ingredients. Halogenated benzoylacetic acid esters (R' is substituted phenyl) are initial products for quinolone and cinnolinecarboxylic acids, which can be used, for example, as antibiotics (e.g., ciprofloxacin).
3-Oxopentanoic acid ester (R' is ethyl) is an important intermediate product for the synthesis of the antiinflammatory active ingredient etodolac.
Numerous methods for the production of 3-oxocarboxylic acid esters have been known for some time. For example, C.R. Hauser and B.E. Hudson, Jr. provide a survey in Orqanic Reactions, Vol. 1, (1942), pages 297 to 302.
In particular, the acylation of malonic esters or acetoacetic acid esters with carboxylic acid chlorides with subsequent cleavage of an ester group or an acetyl group is generally applicable {see, G. Hesse in "Methoden der organischen Chemie" [Methods of Organic Chemistry], 4th ed., Vol. VI/1d, (1978), page 73}.
For reasons of cost, acetoacetic acid ester is to be preferred as the initial material for the production on an industrial scale. In this case, the acetoacetic acid ester is advantageously used in the form of a metal enolate. For this purpose, magnesium enolates, which can easily be produced even in an aqueous medium, are especially suitable [see, e.g. B.M. Conrad, Justus Liebigs Ann. Chem., 188, (1877), pages 269 to 274].
Another advantage of the use of acetoacetic acid esters instead of malonic esters as the initial material is the simpler cleavage, in comparison to acylmalonic esters, of the 2-acyl- acetoacetic acid esters resulting as the intermediate product [see, H. Henecka in "Methoden der organischen Chemie", 4th ed., Vol. VIII, (1952), pages 615 ff], which can take place, for example, with aqueous ammonia.
However, it has been shown that the acylation of acetoacetic acid ester magnesium enolate with carboxylic acid chlorides in practice often leads to unsatisfactory results. Thus, in particular, by-products, such as, diacetoacetic ester, are often obtained, which not only reduce the yield of the desired product but are also difficult to separate and, thus, result in unjustifiable expense in the working up or make the extraction of a pure product completely impossible.
For example, the reworking of the process for the production of pivaloylacetic acid ethyl ester from acetoacetic ester magnesium enolate and pivaloyl chloride, described in published Japanese Published Pat. Application No. 57-70837, yielded only usable yields of about 35 percent and a very unpure product with a content of only about 70 percent.